The objective of this project is to determine how hormones of the pancreatic islet, particularly glucagon and somatostatin, are synthesized so that their secretion and their action is regulating metabolic processes is possible. This goal requires the study of the cellular biosynthesis and the cell-free synthesis of the corresponding hormone precursors, as well as the isolation and chemical characterization of the precursor forms themselves. These complementary approaches will lead to the examination of the mechanisms which might control the proteolytic conversation of the generally inactive precursors to the active product hormones within their tissues of origin. Methods include incubation of tissue with radioactive amino acids to study cellular biosynthesis and extraction of tissue mRNA and cell-free translation to study synthesis in nonprocessing systems. Radioimmunological assays and immunoadsorption are useful in both detecting and purifying hormone-related forms. In addition, a procedure is proposed which might result in the production of tissue enriched in glucagon-producing A-cells for use in studies of the biosynthesis of this hormone.